11-63719394-A-C

Variant names:

• chr11-63719394-A-C
• rs1247048618
• NM_001265589.2:c.892A>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001265589.2(RTN3):​c.892A>C​(p.Arg298Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RTN3 NM_001265589.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.377
• Publications: 0 publications found

Genes affected

RTN3 (HGNC:10469): (reticulon 3) This gene belongs to the reticulon family of highly conserved genes that are preferentially expressed in neuroendocrine tissues. This family of proteins interact with, and modulate the activity of beta-amyloid converting enzyme 1 (BACE1), and the production of amyloid-beta. An increase in the expression of any reticulon protein substantially reduces the production of amyloid-beta, suggesting that reticulon proteins are negative modulators of BACE1 in cells. Alternatively spliced transcript variants encoding different isoforms have been found for this gene, and pseudogenes of this gene are located on chromosomes 4 and 12. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=0.377 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001265589.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN3	NM_001265589.2	MANE Select	c.892A>C	p.Arg298Arg	synonymous	Exon 3 of 9	NP_001252518.1	O95197-1
	RTN3	NM_201428.3		c.835A>C	p.Arg279Arg	synonymous	Exon 2 of 8	NP_958831.1	O95197-2
	RTN3	NM_001265590.2		c.556A>C	p.Arg186Arg	synonymous	Exon 2 of 8	NP_001252519.1	O95197-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RTN3	ENST00000377819.10	TSL:1 MANE Select	c.892A>C	p.Arg298Arg	synonymous	Exon 3 of 9	ENSP00000367050.5	O95197-1
	RTN3	ENST00000339997.8	TSL:1	c.835A>C	p.Arg279Arg	synonymous	Exon 2 of 8	ENSP00000344106.4	O95197-2
	RTN3	ENST00000540798.5	TSL:1	c.556A>C	p.Arg186Arg	synonymous	Exon 2 of 8	ENSP00000442733.1	O95197-7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461880 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727236

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1112002

Other (OTH) AF: 0.0000166 AC: 1 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	6.7
DANN	Benign	0.58
PhyloP100		0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1247048618; hg19: chr11-63486866;